Fig. 6.1
The mechanism of tumour invasion and metastasis
A lack of adhesion between cells facilitates loosening of the tumour cells allowing them to move away from the tumour body. Enzymes secreted by the tumour cells cause local degradation of the basement membrane and interstitial connective tissue. Breach of the basement membrane is the first event in cell invasion. The tumour cells attach to the extracellular matrix proteins causing modification to the matrix that promotes invasion and metastasis and allowing the tumour cells to enter the circulatory system. Tumour cells are quite inefficient at colonising distant organs and most tumour cells circulate as micrometastases undetected in the system for prolonged periods of time.
Extravasation of the tumour cells involves adhesion to the vascular endothelium followed by egression through the basement membrane into the organ parenchyma by mechanisms similar to those involved in invasion.
The site of extravasation and the organ distribution of metastases can be predicted by the site of the primary tumour and its vascular or lymphatic drainage. This may be the first capillary bed they encounter. Other influences may include expression of adhesion molecules by tumour cells whose ligands are expressed preferentially on the endothelium of the target organ. They are also influenced by the expression of proteins that direct movement. Once the cancer cells reach a target the tumour cells must be able to colonise to continue growth. Tumour cells appear to secrete cytokines, growth factors and proteases that act on the resident stromal cells to make the site habitable.
Tumour cells arising in tissue with a rich lymphatic network such as the breast often metastasise by this route. Invasive tumours may penetrate lymphatic channels more readily than blood vessels. Lymph formation occurs at the microscopic level. During the exchange of fluid and molecules between the blood circulation and body tissues, blood capillaries may not reabsorb all of the fluid; surrounding lymphatic capillaries absorb the excess fluid and cancer cells. This is then filtered and carried to the sentinel lymph node and from there to distal nodes and other organs [5].
Breast Cancer
The biology of breast cancer is complicated and little understood making it difficult to predict and manage [4, 6–10]. Breast cancer is a heterogeneous process with very variable appearances, biology and clinical behaviour. However, the cancer cells develop from the epithelium of lobules and ducts.
There are many ways that breast cancer can develop [8] and a theoretical typical progression may be:
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Atypical and In situ disease
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Invasive tumour
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Regional metastases to sentinel lymph nodes
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Involvement of other regional lymph nodes
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Metastatic spread to distant sites
Atypia and In Situ Disease
During this phase tumour growth is restricted to the lobules and ducts which are delineated by a continuous basal membrane and are therefore non-invasive [11]. Although controversial atypical ductal and lobular hyperplasia are often considered to be a precursor or risk indicator for subsequent breast cancers [6, 7]. Lobular carcinoma in situ (LCIS) has cells with the morphology of invasive lobular carcinoma but is contained within the basement membrane. Ductal carcinoma in situ (DCIS) grows within the duct system of the breast and can vary in size and extent. High grade DCIS is a more inherently high-risk disease in terms of progression into invasive breast cancer. All of these conditions are confined within the boundaries of the normal structures of the breast and therefore cannot metastasise [1–3].
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